A Multicenter Trial to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of HZN-825 in Patients With Diffuse Cutaneous Systemic Sclerosis

Study Purpose

This is a randomized, double-blind, placebo-controlled, repeat-dose, multicenter trial. Participants will be screened within 4 weeks prior to the Baseline (Day 1) Visit. Approximately 300 participants who meet the trial eligibility criteria will be randomized on Day 1 in a 1:1:1 ratio to receive HZN-825 300 mg QD, HZN-825 300 mg BID or placebo for 52 weeks. The trial will include up to a 4-week Screening Period and a 52-week Double-blind Treatment Period. Participants will take their first dose of trial drug at the clinic and will return to the clinic for trial visits at Week 4 and every 6 weeks thereafter until Week 52. All participants who complete the Double-blind Treatment Period (Week 52) will be eligible to enter a 52-week extension trial (HZNP-HZN-825-302, NCT not available yet). Participants not entering the extension will return to the clinic for a Safety Follow-up Visit 4 weeks after the last dose of trial drug.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 75 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Written informed consent. 2. Male or female between the ages of 18 and 75 years, inclusive, at Screening. 3. Meets the 2013 American College of Rheumatology/European League Against Rheumatism classification criteria for SSc with a total score of ≥9 (Van den Hoogen et al., 2013). 4. Classified as having skin involvement proximal to the elbow and knee (diffuse cutaneous SSc subset by LeRoy and Medsger, 2001). 5. At the time of enrollment, less than 36 months since the onset of the first SSc manifestation, other than Raynaud's phenomenon. 6. Based on data available through medical history and/or medical records, the subject should have at least 1 of the following: 1. disease duration ≤18 months. 2. increase ≥3 in mRSS units compared with the last visit within the previous 1 month to 6 months. 3. involvement of 1 new body area with ≥2 mRSS units or 2 new body areas with ≥1 mRSS unit. 4. documentation of worsening skin thickening for subjects who did not have mRSS performed during the previous visit. 5. presence of tendon friction rub at Screening. 7. Presence of at least 1 of the following features of elevated acute phase reactants at Screening:
  • - high-sensitivity C-reactive protein (hsCRP) ≥0.6 mg/dL (≥6 mg/L), - erythrocyte sedimentation rate (ESR) ≥28 mm/hr, - platelet count ≥330 × 10^9/L (330,000/μL).
8. Skin thickening from SSc in the forearm suitable for repeat biopsy. 9. mRSS units ≥15 at Screening. 10. FVC ≥45% predicted at Screening, as determined by spirometry. 11. Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial.

Exclusion Criteria:

1. Positive for anti-centromere antibodies. 2. Diagnosed with sine scleroderma or limited cutaneous SSc. 3. Diagnosed with other autoimmune connective tissue diseases, except for fibromyalgia, scleroderma-associated myopathy and secondary Sjogren's syndrome. 4. Scleroderma renal crisis diagnosed within 6 months of the Screening Visit. 5. Any of the following cardiovascular diseases: 1. uncontrolled, severe hypertension (≥160/100 mmHg) or persistent low blood pressure (systolic blood pressure <90 mmHg) within 6 months of Screening, 2. myocardial infarction within 6 months of Screening, 3. unstable cardiac angina within 6 months of Screening. 6. DLCO <40% predicted (corrected for hemoglobin). If severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure is of clinical concern for any subject, consider using a DLCO up to 6 months before the Screening Visit. 7. Pulmonary arterial hypertension (PAH) by right heart catheterization requiring treatment with more than 1 oral PAH-approved therapy or any parenteral therapy. Treatment is allowed for erectile dysfunction and/or Raynaud's phenomenon/digital ulcers. 8. Corticosteroid use for conditions other than SSc within 4 weeks prior to Screening (topical steroids for dermatological conditions and inhaled/intranasal/intra-articular steroids are allowed). 9. Use of any other non-steroid immunosuppressive agent, small biologic molecule, cytotoxic or anti-fibrotic drug within 4 weeks of Screening, including cyclophosphamide, azathioprine (Imuran®) or other immunosuppressive or cytotoxic medication. Exceptions include mycophenolate mofetil (CellCept®), mycophenolic acid (Myfortic®), methotrexate and low-dose prednisone, as follows: use of CellCept ≤3 g/day, Myfortic ≤2.14 g/day, methotrexate ≤15 mg/week and prednisone ≤10 mg/day (or equivalent dosing of glucocorticoids) is allowed. See Table 9.1 for full details. Subjects taking CellCept, Myfortic or methotrexate must have been doing so for ≥6 months and the dose must have been stable for ≥16 weeks prior to the Day 1 Visit. Prednisone must have been at a stable dose for ≥8 weeks prior to the Day 1 Visit. It is acceptable to be on background low-dose prednisone and anti-malarial drug along with CellCept, Myfortic or methotrexate. Rituximab must not have been used within 6 months of the Day 1 Visit. 10. Known active bacterial, viral, fungal, mycobacterial or other infection, including tuberculosis or atypical mycobacterial disease (fungal infections of nail beds are allowed). 11. Use of a United States Food and Drug Administration-approved agent for SSc or an investigational agent for any condition within 90 days or 5 half-lives, whichever is longer, prior to Screening or anticipated use during the course of the trial. 12. Malignant condition in the past 5 years (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ). 13. Women of childbearing potential or male subjects not agreeing to use highly effective method(s) of birth control throughout the trial and for 1 month after last dose of trial drug. Male subjects must refrain from sperm donation and females from egg/ova donation for this same time period. 14. Pregnant or lactating women. 15. Current drug or alcohol abuse or history of either within the previous 2 years, in the opinion of the Investigator or as reported by the subject. 16. Previous enrollment in this trial or participation in a prior HZN-825 or SAR100842 clinical trial. 17. Known history of positive test for human immunodeficiency virus. 18. Active hepatitis (hepatitis B: positive hepatitis B surface antigen and positive anti-hepatitis B core antibody [anti-HBcAb] and negative hepatitis B surface antibody [HBsAb] or positive for HBcAb with a positive test for HBsAb and with presence of hepatitis B virus DNA at Screening; hepatitis C: positive anti-hepatitis C virus [anti-HCV] and positive RNA HCV). 19. Current alcoholic liver disease, primary biliary cirrhosis or primary sclerosing cholangitis. 20. Previous organ transplant (including allogeneic and autologous marrow transplant). 21. International normalized ratio >2, prolonged prothrombin time >1.5 × the upper limit of normal (ULN) or partial thromboplastin time >1.5 × ULN at Screening. 22. Alanine aminotransferase or aspartate aminotransferase >2 × ULN. 23. Estimated glomerular filtration rate <30 mL/min/1.73 m^2 at Screening. 24. Total bilirubin >2 × ULN. Subjects with documented diagnosis of Gilbert's syndrome may be enrolled if their total bilirubin is ≤3.0 mg/dL. 25. Any other condition that, in the opinion of the Investigator, would preclude enrollment in the trial.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04781543
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Horizon Therapeutics Ireland DAC
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Farah Ali, MD
Principal Investigator Affiliation Horizon Therapeutics
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Diffuse Cutaneous Systemic Sclerosis, Sclerosis, Systemic
Arms & Interventions

Arms

Experimental: HZN-825 300 mg once daily (QD)

300mg oral tablets given in the morning and placebo in the evening

Experimental: HZN-825 300 mg twice daily (BID)

300mg oral tablets given in the morning and evening

Placebo Comparator: Placebo

Placebo will be given orally in the morning and evening

Interventions

Drug: - HZN-825 BID

300 mg oral tablets BID

Drug: - Placebo

Placebo BID

Drug: - HZN-825 QD

300 mg oral tablets QD

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

New Orleans, Louisiana

Status

Recruiting

Address

DelRicht Clinical Research, LLC - ClinEdge - PPDS

New Orleans, Louisiana, 70115

Site Contact

Katie Oeland

[email protected]

504-336-2667

Metroplex Clinical Research Center, Dallas, Texas

Status

Recruiting

Address

Metroplex Clinical Research Center

Dallas, Texas, 75231

Site Contact

Tri Nguyen

[email protected]

214-879-6737